BETHESDA, MD-Older cancer
patients should receive adequate
prophylaxis with growth factors to
ensure that they can receive full-dose
chemotherapy without dose reductions,
according to Ralph V. Boccia,
MD.
If doses are reduced or delayed because
of cytopenia, the treatment
might be less successful; in fact, there
are very few cases in which doses for
the fit elderly should be reduced: "You
won't end up with the outcome, and
you will still end up with the toxicity,"
said Dr. Boccia, director of research at
the Center for Cancer and Blood Disorders,
Bethesda, Maryland.
There is ample evidence, he said, to
show that age is not a contraindication
to standard-dose chemotherapy for
lung, breast, colorectal, and prostate
cancer, along with non-Hodgkin's
lymphoma.
Cancer patients more than 65 years
of age are less tolerant of chemotherapy,
and they have a higher risk of
adverse effects such as neutropenia
and anemia. However, fit older patients
who receive adequate prophylaxis
now appear to be able to tolerate
the bone marrow suppression caused
by their treatment.
Benefits of Growth Factors
"There are effective ways to cope
with treatment-related toxic effects,"
said Dr. Boccia. For example, multiple
trials have shown that hematopoietic
growth factors reduce the incidence of
neutropenia, and more importantly
neutropenic infections, vs no administration
of growth factors.
In proposed guidelines, expertsrecommended that patients aged 70
years or older receive hematopoietic
growth factors such as filgrastim in
any combination chemotherapy regimen
that has dose intensity equivalent
to CHOP (cyclophosphamide
[Cytoxan, Neosar]/doxorubicin HCl/
vincristine [Oncovin]/prednisone) or
AC (doxorubicin/cyclophosphamide).
In addition, the experts say
hemoglobin (Hb) should be maintained
at 12 g/dL or above with erythropoietic
agents (Oncology 14:221-
227, 2000).
For elderly patients, erythropoietic
agents can help ameliorate fatigue,
complications of anemia and chemotherapy
toxicity. Studies (J Clin Oncol
19:2865-2874, 2001) have shown that
correcting anemia this way may improve
survival in cancer patients.
Erythropoietic agents also have
been shown to improve quality of life
in multiple studies, including a study
by Glaspy et al (The Oncologist 7:126-
135, 2002), in which investigators
looked at Functional Assessment of
Cancer Therapy-Anemia (FACT-An)
scores relative to Hb improvement in
more than 4,000 community-treated
cancer patients receiving epoetin alfa
(Procrit). Glaspy et al found that even
small increases in Hb yielded improvements
in quality of life. "This can even
occur in patients with progressive dis-ease, if you correct anemia, which is
pretty striking," Dr. Boccia said.
CHOP-14 Plus G-CSF Superior
to CHOP-21
Elderly patients may also benefit
from dose intensification enabled by
use of growth factors. This was shown
in a trial by the German High-Grade
Non-Hodgkin's Lymphoma Study
Group (DSHNHL) that suggested that
the 14-day CHOP regimen could become
the new standard regimen for
NHL patients more than 60 years of
age.
In the DSHNHL trial, presented at
the 2001 meeting of the American Society
of Hematology (abstract 3027),
investigators randomized more than
807 elderly patients (age range, 61 to
75 years) with aggressive NHL to 6
cycles of the typical CHOP-every-21-
days schedule (CHOP-21), or one of
three comparator arms: CHOP every
21 days plus etoposide (CHOEP-21);
dose-intensive CHOP every 14 days
(CHOP-14) plus granulocyte colonystimulating
factor (G-CSF [Neupogen])
support; or dose-intensive
CHOP plus etoposide every 14 days
(CHOEP-14) plus G-CSF support.
Relative dose intensities were 95%
for CHOEP-21 and 93% for CHOP-
14 plus. "Clearly, they were able to
maintain dose intensity [by] giving
cytokine therapy [with] these two regimens,"
Dr. Boccia said.
For standard CHOP-21, the complete
response rate was 63.2%, compared
with 77% for dose-intense
CHOP-14 with G-CSF support (P =
.009). At a median of 40 months' observation
time, overall survival was
49% for CHOP-21 and 64.3% for
CHOP-14 (P = .04).
"What was impressive was that the
response rate looked quite good," said
Dr. Boccia. "If you intensify using cytokine
support, the response rate is
higher and overall survival appears to
be up."

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